Introduction

Historic drawing of the fetal male urogenital system

In humans, the male accessory glands are the seminal vesicles, prostate gland, and the bulbourethral glands. The male gonad, the testis, differentiates embryonically initially under the influence of the Y chromosome. Later under the influence the gonad-derived fetal testosterone acting through androgen receptors, a region of the urogenital sinus (UGS) mesenchyme differentiates to form the primordial prostate buds. The buds then signal back to the overlying epithelium, inducing duct formation, this was one of the early studied (1970's) example of an mesenchymal-epithelial interaction in development. Interestingly, the female equivalent gland originally called Skene's gland, then paraurethral gland has now also been renamed the female prostate.

The reproductive function of the prostate becomes active at puberty where prostate secretions contribute the majority by volume of the ejaculate containing spermatozoa.

The prostate gland is generally in the news due to its late postnatal adult growth changes, enlarged due to benign nodular hyperplasia, and the male health effects of prostate cancer. Prostate cancer is the second most common malignant tumor in western males and anatomically involves the prostate peripheral zone.

Some Recent Findings

Male urogenital development (stage 22)

Maternal protein malnutrition: effects on prostate development and adult disease[1] "Well-controlled intrauterine development is an essential condition for many aspects of normal adult physiology and health. This process is disrupted by poor maternal nutrition status during pregnancy. Indeed, physiological adaptations occur in the fetus to ensure nutrient supply to the most vital organs at the expense of the others, leading to irreversible consequences in tissue formation and differentiation. Evidence indicates that maternal undernutrition in early life promotes changes in key hormones, such as glucocorticoids, growth hormones, insulin-like growth factors, estrogens and androgens, during fetal development. These alterations can directly or indirectly affect hormone release, hormone receptor expression/distribution, cellular function or tissue organization, and impair tissue growth, differentiation and maturation to exert profound long-term effects on the offspring. Within the male reproductive system, maternal protein malnutrition alters development, structure, and function of the gonads, testes and prostate gland. Consequently, these changes impair the reproductive capacity of the male offspring. Further, permanent alterations in the prostate gland occur at the molecular and cellular level and thereby affect the onset of late life diseases such as prostatitis, hyperplasia and even prostate cancer. This review assembles current thoughts on the concepts and mechanisms behind the developmental origins of health and disease as they relate to protein malnutrition, and highlights the effects of maternal protein malnutrition on rat prostate development and homeostasis. DOHAD

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development[2] "It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. ...In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells."

The role of Wnt5a in prostate gland development[4] "The Wnt genes encode a large family of secreted glycoproteins that play important roles in controlling tissue patterning, cell fate and proliferation during development. Currently, little is known regarding the role(s) of Wnt genes during prostate gland development. The present study examines the role of the noncanonical Wnt5a during prostate gland development in rat and murine models. In the rat prostate, Wnt5a mRNA is expressed by distal mesenchyme during the budding stage and localizes to periductal mesenchymal cells with an increasing proximal-to-distal gradient during branching morphogenesis. Wnt5a protein is secreted and localizes to periductal stroma, extracellular matrix and epithelial cells in the distal ducts. While Wnt5a expression is high during active morphogenesis in all prostate lobes, ventral prostate (VP) expression declines rapidly following morphogenesis while dorsal (DP) and lateral lobe (LP) expression remains high into adulthood. Steroids modulate prostatic Wnt5a expression during early development with testosterone suppressing Wnt5a and neonatal estrogen increasing expression."

More recent papers

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Genital Development Overview

Three main stages during development, mesonephric/paramesonephric duct changes are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while.

Differentiation of gonad (Sex determination)

Differentiation of internal genital organs

Differentiation of external genital organs

The 2nd and 3rd stages dependent on endocrine gonad. Reproductive development has a long maturation timecourse, begining in the embryo and finishing in puberty. (More? Puberty Development)

Mouse Prostate Development

The mouse has been used extensively as a model of prostate embryonic development. A similar androgenic regulation occurs of in ventral epithelial bud affecting number and pattern forming in the mouse urogenital sinus.[7]

Anatomy

The prostate is the largest accessory sex gland in men (about 2 × 3 × 4 cm). It contains 30 - 50 tubuloalveolar glands, which empty into 15 - 25 independent excretory ducts. These ducts open into the urethra. The glands are embedded into a fibromuscular stroma, which mainly consists of smooth muscle separated by strands of connective tissue rich in collagenous and elastic fibres. The muscle forms a dense mass around the urethra and beneath the fairly thin capsule of the prostrate.

Macroscopically the prostrate can be divided into lobes, but they are inconspicuous in histological sections. In good histological sections it is possible to distinguish three concentric zones, which surround the prostatic part of the urethra.

peripheral zone contains large (main glands) whose ducts run posteriorly to open into the urethra

internal zone consists of the so-called submucosal glands

innermost zone contains mucosal glands

Secretory Glands

The secretory alveoli of the prostate are very irregularly shaped because of papillary projections of the mucosa into the lumen of the gland. The epithelium is cuboidal or columnar. Basal cells are again present, and the epithelium may look pseudostratified where they are found. The secretory cells are slightly acidophilic and secretory granules may be visible in the cytoplasm. Small extensions of the apical cytoplasm into the lumen of the alveoli may represent cells which release their secretory products (secretion is apocrine/merocine). The secretion of the prostate contains citric acid, the enzyme fibrinolysin (liquefies the semen), acid phosphatase, a number of other enzymes and lipids. The secretion of the prostate is the first fraction of the ejaculate.

The secretory ducts of the prostate are lined by a simple columnar epithelium, which changes to a transitional epithelium near the openings of the ducts into the urethra.

Corpora Amylacea

A characteristic feature of the prostate is the appearance of corpora amylacea in the secretory alveoli. They are rounded eosinophilic bodies. Their average diameter is about 0.25 mm (up to 2 mm). They appear already in the seventh month of foetal development. Their number increases with age - in particular past 50. They may undergo calcification. Corpora amylacea may appear in semen.

Historic Gray's Anatomy - The Prostate

The prostate (Fig. 1160) is a firm, partly glandular and partly muscular body, which is placed immediately below the internal urethral orifice and around the commencement of the urethra. It is situated in the pelvic cavity, below the lower part of the symphysis pubis, above the superior fascia of the urogenital diaphragm, and in front of the rectum, through which it may be distinctly felt, especially when enlarged. It is about the size of a chestnut and somewhat conical in shape, and presents for examination a base, an apex, an anterior, a posterior and two lateral surfaces.

The base (basis prostatæ) is directed upward, and is applied to the inferior surface of the bladder, The greater part of this surface is directly continuous with the bladder wall; the urethra penetrates it nearer its anterior than its posterior border.

The apex (apex prostatæ) is directed downward, and is in contact with the superior fascia of the urogenital diaphragm.

Surface

The posterior surface (facies posterior) is flattened from side to side and slightly convex from above downward; it is separated from the rectum by its sheath and some loose connective tissue, and is distant about 4 cm. from the anus. Near its upper border there is a depression through which the two ejaculatory ducts enter the prostate. This depression serves to divide the posterior surface into a lower larger and an upper smaller part. The upper smaller part constitutes the middle lobe of the prostate and intervenes between the ejaculatory ducts and the urethra; it varies greatly in size, and in some cases is destitute of glandular tissue. The lower larger portion sometimes presents a shallow median furrow, which imperfectly separates it into a right and a left lateral lobe: these form the main mass of the gland and are directly continuous with each other behind the urethra. In front of the urethra they are connected by a band which is named the isthmus: this consists of the same tissues as the capsule and is devoid of glandular substance.

The anterior surface (facies anterior) measures about 2.5 cm. from above downward but is narrow and convex from side to side. It is placed about 2 cm. behind the pubic symphysis, from which it is separated by a plexus of veins and a quantity of loose fat. It is connected to the pubic bone on either side by the puboprostatic ligaments. The urethra emerges from this surface a little above and in front of the apex of the gland.

The lateral surfaces are prominent, and are covered by the anterior portions of the Levatores ani, which are, however, separated from the gland by a plexus of veins.

The prostate measures about 4 cm. transversely at the base, 2 cm. in its antero-posterior diameter, and 3 cm. in its vertical diameter. Its weight is about 8 gm. It is held in its position by the puboprostatic ligaments; by the superior fascia of the urogenital diaphragm, which invests the prostate and the commencement of the membranous portion of the urethra; and by the anterior portions of the Levatores ani, which pass backward from the pubis and embrace the sides of the prostate. These portions of the Levatores ani, from the support they afford to the prostate, are named the Levatores prostatæ.

The prostate is perforated by the urethra and the ejaculatory ducts. The urethra usually lies along the junction of its anterior with its middle third. The ejaculatory ducts pass obliquely downward and forward through the posterior part of the prostate, and open into the prostatic portion of the urethra.

Structure

The prostate is immediately enveloped by a thin but firm fibrous capsule, distinct from that derived from the fascia endopelvina, and separated from it by a plexus of veins. This capsule is firmly adherent to the prostate and is structurally continuous with the stroma of the gland, being composed of the same tissues, viz.: non-striped muscle and fibrous tissue. The substance of the prostate is of a pale reddish-gray color, of great density, and not easily torn. It consists of glandular substance and muscular tissue.

The muscular tissue according to Kölliker, constitutes the proper stroma of the prostate; the connective tissue being very scanty, and simply forming between the muscular fibers, thin trabeculæ, in which the vessels and nerves of the gland ramify. The muscular tissue is arranged as follows: immediately beneath the fibrous capsule is a dense layer, which forms an investing sheath for the gland; secondly, around the urethra, as it lies in the prostate, is another dense layer of circular fibers, continuous above with the internal layer of the muscular coat of the bladder, and blending below with the fibers surrounding the membranous portion of the urethra. Between these two layers strong bands of muscular tissue, which decussate freely, form meshes in which the glandular structure of the organ is imbedded. In that part of the gland which is situated in front of the urethra the muscular tissue is especially dense, and there is here little or no gland tissue; while in that part which is behind the urethra the muscular tissue presents a wide-meshed structure, which is densest at the base of the gland—that is, near the bladder—becoming looser and more sponge-like toward the apex of the organ.

The glandular substance is composed of numerous follicular pouches the lining of which frequently shows papillary elevations. The follicles open into elongated canals, which join to form from twelve to twenty small excretory ducts. They are connected together by areolar tissue, supported by prolongations from the fibrous capsule and muscular stroma, and enclosed in a delicate capillary plexus. The epithelium which lines the canals and the terminal vesicles is of the columnar variety. The prostatic ducts open into the floor of the prostatic portion of the urethra, and are lined by two layers of epithelium, the inner layer consisting of columnar and the outer of small cubical cells. Small colloid masses, known as amyloid bodies are often found in the gland tubes.

Vessels and Nerves

The arteries supplying the prostate are derived from the internal pudendal, inferior vesical, and middle hemorrhoidal. Its veins form a plexus around the sides and base of the gland; they receive in front the dorsal vein of the penis, and end in the hypogastric veins. The nerves are derived from the pelvic plexus.

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Abnormalities

Benign Nodular Hyperplasia

A postnatal adult ageing effect with an onset about 45 years of age, the prostate becomes enlarged due to benign nodular hyperplasia. By 60 years of age and older about 3/4 of the males are affected of which half will be symptomatic. This condition affects the mucosal glands.

Prostate Cancer

Prostate cancer is the second most common malignant tumor in western males and anatomically involves the prostate peripheral zone.

The dog has been used as a model of this condition as this species also spontaneously develop prostatic neoplasia. The cell line CT1258 has been derived from a spontaneous canine prostate carcinoma and can induce tumour formation in mice.

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